Processes and systems for preparing cellular or viral membranes and nanoparticles
The present invention relates to processes and systems for preparing nanoparticles, cellular or viral membranes and/or cellular or viral membrane coated nanoparticles using or comprising, inter alia, a multi-inlet vortexing reactor, tangential flow filtration (TFF) and/or a high shear fluid processor such as a microfluidizer (or a microfluidizer processor). The present invention also relates to the nanoparticles, cellular or viral membranes and/or cellular or viral membrane coated nanoparticles prepared by the present processes and systems, and the uses and/or applications of the nanoparticles, cellular or viral membranes and/or cellular or viral membrane coated nanoparticles.
1. A process for preparing a cellular membrane coated nanoparticle, which process comprises mixing a nanoparticle inner core comprising a non-cellular material with a plasma membrane derived from a cell, said plasma membrane comprising a receptor activity and/or an enzymatic activity of said plasma membrane, using a high shear fluid processor to form a plasma membrane coated nanoparticle comprising said inner core and an outer surface comprising said plasma membrane,
wherein said inner core supports said outer surface, and said plasma membrane coated nanoparticle substantially maintains said receptor activity and/or enzymatic activity.
2. The process of claim 1 , wherein the inner core comprises a material selected from the group consisting of:
1) a biocompatible material,
2) a biocompatible and synthetic material,
3) poly(lactic-co-glycolic acid) (PLGA),
4) polylactic acid (PLA),
5) polyglycolic acid (PGA),
6) polycaprolactone (PCL),
7) polylysine, polyglutamic acid, and
8) a hydrophobic polymer that coils when switched from an organic solvent to an aqueous phase.
3. The process of claim 1 , wherein the cellular membrane comprises a plasma membrane derived from a red blood cell.
4. The process of claim 1 , wherein the nanoparticle substantially lacks constituents of the cell from which the plasma membrane is derived.
5. The process of claim 1 , wherein the high shear fluid processor comprises a microchannel and the high shear fluid processor is configured to generate an average velocity that is up to about 500 meter/second (mis) in the microchannel.
6. The process of claim 1 , wherein the high shear fluid processor is a microfluidizer or a homogenizer that generates high shear force.
7. The process of claim 6 , wherein the high shear fluid processor is a microfluidizer that has the microfluidics reaction technology (MRT) configuration that comprises, from upstream to downstream, an inlet for inputting a nanoparticle inner core comprising a non-cellular material and/or a plasma membrane derived from a cell, an intensifier pump for generating a static pressure, an impinging jet chamber for generating a high shear pressure on a mixture of the nanoparticle inner core and the plasma membrane to form a plasma membrane coated nanoparticle, and an outlet for outputting the plasma membrane coated nanoparticle.
8. The process of claim 1 , which is used to prepare the plasma membrane coated nanoparticle at a production rate ranging from about 0.1 g/hour to about 1,500 g/hour for one production batch.
9. The process of claim 1 , which further comprises assessing the receptor activity and/or an enzymatic activity of the plasma membrane coated nanoparticle.
10. The process of claim 1 , wherein the cellular membrane comprises a plasma membrane derived from a red blood cell and the nanoparticle substantially lacks hemoglobin.